# Tubulopathy

Tubulopathy is a disease affecting the renal tubules of the nephron.
Tubulopathic processes may be inflammatory or noninflammatory, though inflammatory processes are often referred to specifically as tubulitis.
Characteristics of Some Inherited Tubulopathies :
| Disorder [OMIM Number] | Protein Defect | Chromosome Localization | Inheritance | Clinical Features/Notes | Biochemical Features |
| Proximal Tubule | | | | | |
| Lowe's syndrome (oculocerebral dystrophy [309000] | OCRL1 | Xq26.1 | XR | Hydrophthalmia, cataract, mental retardation, hyporeflexia, hypotonia and progressive kidney failure, normotensive | Plasma: ↓K, ↓CO$_2$; Urine: ↑LMWP, ↑AA, ↑PO$_4$, ↑K |
| Wilson's disease [277900] | ATP7B | 13q14.3-q21.1 | AR | Liver disease or neurologic symptoms, or both, Kayser–Fleischer rings, normotensive | Plasma: ↑free copper, abnormal LFTs; Urine: ↑copper excretion, ↑LMWP, ↑AA, ↑PO$_4$, ↑Glycosuria |
| Dent's disease (X-linked recessive hypophophatemic rickets)[300009] | CLCN5 | Xp11.22 | XR | Nephrocalcinosis, nephrolithiasis, rachitic and osteomalacic bone disease, progressive kidney failure, normotensive | Plasma: ↓PO$_4$, N/↓K; Urine: ↑LMWP, ↑AA, ↑K, ↑Ca, ↑PO$_4$, ↑Glycosuria |
| X-linked dominant hypophosphatemic rickets [307800 | PHEX | Xp22.2-p22.1 | XD | Growth retardation, rachitic and osteomalacic bone disease, hypophosphatemia, and renal defects in phosphate reabsorption and vitamin D metabolism | Plasma: ↓PO$_4$, ↑ALP; Urine: ↑PO$_4$ |
| Loop of Henle | | | | | |
| Bartter's syndrome | NKCC2 (type 1) | 15q15-21.1 | AR | Polyuria, polydipsia, muscle weakness, hypovolemia, normotensive or hypotensive (all types). Maternal polyhydramnios, premature birth, perinatal salt wasting, nephrocalcinosis and kidney stones (type 1 and 2), milder phenotype with normocalciuria(type 3), sensorineural deafness, motor retardation, renal failure (type 4) | Plasma: ↑renin, ↓K, ↑CO$_2$, mild ↓Mg in some patients; Urine: ↑Ca |
| [601678] | ROMK (type 2) | 11q24 | AR | Polyuria, polydipsia, muscle weakness, hypovolemia, normotensive or hypotensive (all types). Maternal polyhydramnios, premature birth, perinatal salt wasting, nephrocalcinosis and kidney stones (type 1 and 2), milder phenotype with normocalciuria(type 3), sensorineural deafness, motor retardation, renal failure (type 4) | |
| [241200] | C1C-Kb (type 3, classic) | 1p36 | AR | Polyuria, polydipsia, muscle weakness, hypovolemia, normotensive or hypotensive (all types). Maternal polyhydramnios, premature birth, perinatal salt wasting, nephrocalcinosis and kidney stones (type 1 and 2), milder phenotype with normocalciuria(type 3), sensorineural deafness, motor retardation, renal failure (type 4) | |
| [607364] | | 1p31 | AR | Polyuria, polydipsia, muscle weakness, hypovolemia, normotensive or hypotensive (all types). Maternal polyhydramnios, premature birth, perinatal salt wasting, nephrocalcinosis and kidney stones (type 1 and 2), milder phenotype with normocalciuria(type 3), sensorineural deafness, motor retardation, renal failure (type 4) | |
| [602522] | Barttin (type 4) | | | Polyuria, polydipsia, muscle weakness, hypovolemia, normotensive or hypotensive (all types). Maternal polyhydramnios, premature birth, perinatal salt wasting, nephrocalcinosis and kidney stones (type 1 and 2), milder phenotype with normocalciuria(type 3), sensorineural deafness, motor retardation, renal failure (type 4) | |
| Hypomagnesemic hypercalciuric nephrocalcinosis (magnesium-losing kidney)[248250] | PCLN1 | 3q27 | AR | Nephrocalcinosis, renal failure, ocular/hearing defects, polyruria, polydipsia, recurrent urinary tract infections, recurrent renal colic, normotensive | Plasma: ↓Mg, ↑PTH; Urine: ↑Ca, ↑Mg |
| Distal Tubule/Collecting Duct | | | | | |
| Liddle's syndrome [177200] | ENaC (activating) | 16p13-p12 | AD | Early, and frequently severe, hypertension, stroke | Plasma: ↓renin, ↓K, ↓Mg, ↑CO$_2$; Urine: ↑K |
| Pseudohypoaldosteronism type 1a [264350] | ENaC (inactivating) | 12p13, 16p13-p12 | AR | Presents in infancy with salt-wasting and hypotension, Cough, respiratory infections | Plasma: ↑renin, ↓Na, ↑K, ↓CO$_2$; Urine: ↑K |
| Pseudohypoaldosteronism type 1b [177735] | Mineralocorticoid receptor | 4q31.1 | AD | Presents in infancy with salt-wasting and hypotension. Milder than type 1a and remits with age | Plasma: ↑renin, ↓Na, ↑K, ↓CO$_2$; Urine: ↑K |
| Pseudohypoaldosteronism type 2 (Gordon's syndrome) [145260] | Unknown (?WNK) | 1q31-q42, 12p13, 17q21-q22 | AD | Hypertension (± muscle weakness, short stature, intellectual impairment). Correction of physiologic abnormalities by thiazide diuretics | Plasma: ↓renin, ↑K, ↓CO$_2$, ↑Cl; Urine: ↓K |
| Gitelman's syndrome [263800] | NCCT | 16q13 | AR | Hypotension, weakness, paresthesias, tetany, fatigue, and salt craving, Presentation generally much later in life than in Bartter's and hypocalciuria is typical | Plasma: ↑renin, ↓K, ↓Mg, ↑CO$_2$; Urine: ↓calcium:creatinine excretion ratio (useful in distinguishing Gitelman's and Bartter's)(Note: biochemically can mimic thiazide use) |
| X-linked nephrogenic diabetes insipidus type 1 [304800] | V2 receptor | Xq28 | XR | Hyperthermia, polyuria, polydipsia, dehydration, inability to form concentrated urine, intellectual disability if diagnosis delayed. Symptoms in infancy | Hyperosmolar plasma, dilute urine |
| Autosomal dominant nephrogenic diabetes insipidus type 2 [192340] | AQP2 | 12q13 | AD and AR | Polyuria, polydipsia, dehydration, inability to form concentrated urine. Symptoms after first year of life | Hyperosmolar plasma, dilute urine |
AA: Aminoaciduria; AD:autosomal dominant; AR: autosomal recessive; LFT's: Liver function tests; LMWP: low molecular weight proteinuria; XD: X-linked dominant; XR: X-linked recessive; PTH: Parathyroid hormone